Abstract：
:It is now well-recognized that human environmental exposures are not to single chemicals. Rather, humans are exposed, either concurrently or sequentially, to multiple chemicals. Challenges that chemical mixtures pose for risk assessment and toxicology are presented. Challenge areas include increasing the peer-reviewed publication of human studies, improving access to peer-reviewed data and examining multiple target organs. Two difficult challenges are development of a common, consistent language and the use of appropriate and innovative experimental designs and analyses. The challenge of elucidation of mechanism(s) offers a rational basis for extrapolation across dose levels, exposure durations and exposure routes as well as to other species and to other similar chemicals. Of particular importance is focusing effort on those areas of investigation where answers have the greatest potential for reducing uncertainty in risk assessments for chemical mixtures and on those chemical mixtures and multiple chemical exposures that have the greatest potential impact on human health. A particularly fruitful area for future investigation is determination of the likelihood of nonadditive interactions in humans exposed to multiple chemicals at environmental exposure levels.
journal_name
Toxicologyjournal_title
Toxicologyauthors
Simmons JEdoi
10.1016/0300-483x(95)03205-tsubject
Has Abstractpub_date
1995-12-28 00:00:00pages
111-9issue
2-3eissn
0300-483Xissn
1879-3185pii
0300-483X(95)03205-Tjournal_volume
105pub_type
杂志文章相关文献
TOXICOLOGY文献大全abstract：:Gender is a factor that influences susceptibility of individuals to drug-induced liver injury in experimental animals and humans. In this study, we investigated the mechanisms underlying resistance of female mice to acetaminophen (APAP)-induced hepatotoxicity. Overnight-fasted male and female CD-1 mice were administer...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/j.tox.2011.05.018
更新日期：2011-09-05 00:00:00
abstract：:An increasing body of data has been demonstrating that mammalian cells have elaborate networks of molecular signalling in counteracting heat shock and in developing adaptation to oxidative stress to avoid cell death. However, the precise mechanisms linking heat shock, oxidative stress and cell survival/cell death mech...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/j.tox.2006.04.028
更新日期：2006-07-25 00:00:00
abstract：:The urinary metabolites from repeated oral doses of 3.7 mg o-phenyl phenol (OPP) to mature and immature dogs and cats were studied. At both age levels, dogs excreted significantly more OPP as sulfate and glucuronide than did cats. Puppies produced 4 times the level of glucuronides than mature dogs. No such age differe...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/0300-483x(80)90016-5
更新日期：1980-01-01 00:00:00
abstract：:Mutagenicity analysis of urine from rats treated by oral gavage with MX at a dose of 64 mg/kg for 14 days revealed that only 0.3% of the administered compound was excreted in a genotoxically active form. At lower doses, mutagenicity was not detectable. No evidence of micronucleus induction in peripheral blood erythroc...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/0300-483x(96)03336-7
更新日期：1996-06-17 00:00:00
abstract：:Preclinical drug safety assessment includes in vitro studies with physiologically relevant cell cultures. As an in vitro system for hepatic toxicology testing, we have been generating cell clones of human hepatoblastoma cell line HepG2 by lentiviral transduction of phase I cytochrome P450 (CYP) enzymes. Here, we prese...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/j.tox.2018.11.008
更新日期：2019-01-15 00:00:00
abstract：:The susceptibility to hepatocellular carcinoma (HCC) varies greatly within human populations in response to environmental risk agents. The mechanisms underlying differential susceptibility are still largely unknown and need to be clarified to improve HCC chemoprevention and therapeutic treatment. Inbred rodent strains...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/j.tox.2008.09.013
更新日期：2008-12-05 00:00:00
abstract：:Insulin and dexamethasone are potent inhibitors of apoptosis induced by transforming growth factor-beta1 (TGF-beta) in hepatoma cells. Using FTO-2B rat hepatoma cells, we determined whether the anti-apoptotic effects of these agents result from interference within or upstream of the TGF-beta-induced caspase cascade. A...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/j.tox.2004.06.020
更新日期：2004-11-15 00:00:00
abstract：:N-(3,5-Dichlorophenyl)succinimide (NDPS) is an agricultural fungicide which has been shown to induce acute tubular necrosis. The purpose of the present study was to determine if creatinine clearance was altered early in the development of NDPS nephrotoxicity. This study also examined the effect of autacoid modulation ...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/0300-483x(91)90007-n
更新日期：1991-01-01 00:00:00
abstract：:Adrenocortical carcinoma (ACC) is an extremely rare and aggressive endocrine malignancy with a poor prognosis. The most common symptom of ACC is hypercortisolism (Cushing's syndrome), which has the highest mortality. Mitotane is used as a steroidogenesis inhibitor for Cushing's syndrome or as a chemical adrenalectomy ...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/j.tox.2012.04.007
更新日期：2012-08-16 00:00:00
abstract：:In the present work was analyzed whether sulforaphane (SFN) may protect against cisplatin (CIS)-induced hepatic damage, oxidant stress and mitochondrial dysfunction. Four groups of male Wistar rats were studied: control, CIS, CIS+SFN and SFN. SFN was given i.p. (500 μg/kg/d × 3 days) before CIS administration (single ...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/j.tox.2011.04.014
更新日期：2011-08-15 00:00:00
abstract：:Arsenic is an endocrine disruptor that promotes breast cancer (BCa) development. Estrogen synthesis, through aromatase activation, is essential for BCa promotion and progression through activating the G-coupled estrogen receptor 1 (GPER1), regulating rapid nongenomic effects involved in cell proliferation and migratio...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/j.tox.2020.152440
更新日期：2020-05-15 00:00:00
abstract：:The toxicity of daily subcutaneously applied 500 mg/kg N-methylformamide (NMF) during a period of 8 days in female CD-mice was ameliorated when 100 mg/kg sodium ascorbate, 60 mg/kg menadione bisulfite or 80 mg/kg pyridoxal hydrochloride were applied simultaneously. The comparison of the daily s.c. application of 360 m...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/0300-483x(87)90008-4
更新日期：1987-02-01 00:00:00
abstract：:Drug-induced hepatotoxicity is a major problem in drug development, and oxidative stress is known as one of the causes. Superoxide dismutases (SODs) are important antioxidant enzymes against reactive oxygen species (ROS). Mitochondria are the major source of superoxide production, and SOD2 is mainly localized in mitoc...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/j.tox.2009.07.017
更新日期：2009-10-01 00:00:00
abstract：:Cardiac fibrosis is characterized by net accumulation of extracellular matrix (ECM) proteins in the cardiac interstitium, and contributes to both systolic and diastolic dysfunction in many cardiac pathophysiologic conditions. More specifically, cardiac fibroblasts are activated by a variety of pathological stimuli, th...
journal_title：Toxicology
pub_type： 杂志文章,评审
doi：10.1016/j.tox.2014.07.002
更新日期：2014-09-02 00:00:00
abstract：:The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) is an acute nephrotoxicant in rats. Our previous studies have strongly suggested that glucuronide conjugation of NDPS metabolites might be a bioactivation step mediating NDPS nephrotoxicity. In this study, effects of substrates and/or inhibitors of pr...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/s0300-483x(98)00140-1
更新日期：1999-01-01 00:00:00
abstract：:This study investigated the effect of astaxanthin (ASX; 3,3-dihydroxybeta, beta-carotene-4,4-dione), a water-dispersible synthetic carotenoid, on liver ischemia-reperfusion (IR) injury. Astaxanthin (5 mg/kg/day) or olive oil was administered to rats via intragastric intubation for 14 consecutive days before the induct...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/j.tox.2009.11.003
更新日期：2010-01-12 00:00:00
abstract：:Bisphenol A has been shown to affect the reproduction of male rats and mice. However, the mechanism of action of bisphenol A on the epididymal sperm is not elucidated. The present study was undertaken to evaluate the effect of bisphenol A on the antioxidant system of rat epididymal sperm. Bisphenol A was administered ...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/s0300-483x(02)00597-8
更新日期：2003-03-14 00:00:00
abstract：:Recently it has become clear that exposure to xenobiotics may result in various forms of cell death; not only passive cell deaths like necrosis, or programmed cell deaths such as apoptosis, but also regulated necrosis, autophagy, senescence, or mitotic catastrophe. Complex cell signaling networks influence the process...
journal_title：Toxicology
pub_type： 杂志文章,评审
doi：10.1016/j.tox.2012.12.014
更新日期：2013-02-08 00:00:00
abstract：:Phensuximide (PSX) is an antiepileptic agent which has been shown to induce hemorrhagic cystitis and mild nephrotoxicity following repeated administration in man or rats or when acutely administered to phenobarbital-pretreated rats. The purpose of this study was to explore the role of para-hydroxylation of the phenyl ...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/0300-483x(92)90045-g
更新日期：1992-08-01 00:00:00
abstract：:Recent attention to methanol (MeOH) as a potential alternative fuel prompted an evaluation of the chemical's effects during early pregnancy. Rats were dosed by gavage during Days 1-8 of pregnancy at 0, 1.6, 2.4, or 3.2 g MeOH/kg/day. Groups of animals were killed on Days 9, 11, or 20 of pregnancy, and maternal, embryo...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/0300-483x(93)90212-b
更新日期：1993-05-24 00:00:00
abstract：:The combined effects of ethyl alcohol (ETOH) intoxication and carbon monoxide (CO) poisoning were studied in the Levine-prepared rat. Infusion or injection of ETOH before and during 90 min of CO exposure to blood levels 2-4 times those considered legally drunk in humans, increased survival at 2400 ppm, and extended th...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/0300-483x(90)90111-s
更新日期：1990-05-31 00:00:00
abstract：:The presence of inclusion bodies in renal proximal tubules was studied in rats exposed to lead and/or disulfiram (tetraethylthiuram disulfide). Pregnant rats were treated with only lead acetate (0.25% Pb in the drinking water), only disulfiram (0.1 mmol/kg p.o. twice a week) or with both lead acetate and disulfiram fr...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/0300-483x(87)90046-1
更新日期：1987-04-01 00:00:00
abstract：OBJECTIVE:Endothelins (ET) can be considered stress-responsive regulators working in paracrine and autocrine fashion. It has been suggested that elevated levels of ET may be responsible for the low coronary re-flow phenomena. Ischemia-reperfusion (I/R) was shown to stimulate ET release in rat heart; however, the mechan...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/j.tox.2005.11.022
更新日期：2006-02-15 00:00:00
abstract：:Toxicity and other relevant data for 30 organophosphate pesticides were evaluated to suggest inhalation occupational exposure limits (OELs), and to support development of a risk assessment strategy for organophosphates in general. Specifically, the value of relative potency analysis and the predictability of inhalatio...
journal_title：Toxicology
pub_type： 杂志文章,评审
doi：10.1016/s0300-483x(00)00219-5
更新日期：2000-09-07 00:00:00
abstract：:Repeated abuse of stimulant drugs, cocaine and amphetamine, is associated with extraneuronal dopamine accumulation in specific brain areas. Dopamine may be cytotoxic through the generation of reactive oxygen species, namely hydrogen peroxide (H2O2), resulting from dopamine oxidative metabolism. In this work, we studie...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/j.tox.2005.08.022
更新日期：2006-01-05 00:00:00
abstract：:Catecholamines are stress hormones and sympathetic neurotransmitters essential for control of cardiac function and metabolism. However, pathologically increased catecholamine levels may be cardiotoxic by mechanism that includes iron-catalyzed formation of reactive oxygen species. In this study, five iron chelators use...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/j.tox.2011.08.006
更新日期：2011-11-18 00:00:00
abstract：:The effect of potassium cyanide on mitochondria DNA (mtDNA) in mouse brain was investigated in vivo and in vitro. When potassium cyanide (0, 0.1, 1.0 or 2.0 mM) was incubated with a crude mitochondria fraction prepared from mouse brain at 37 degrees C for 60 min, the damage of mtDNA was observed in a concentration-dep...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/s0300-483x(02)00244-5
更新日期：2002-09-30 00:00:00
abstract：:Heavy metal environmental pollutants increase susceptibility of affected individuals to bacterial and viral infections, but the mechanisms responsible for this effect are not known. We established cellular in vitro systems to identify molecular targets for the action of heavy metal ions. We used two model systems to d...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/s0300-483x(01)00483-8
更新日期：2001-12-01 00:00:00
abstract：:Leflunomide, used for the treatment of rheumatoid arthritis, has been reported to cause severe liver problems and liver failure; however, the underlying mechanisms are not clear. In this study, we used multiple approaches including genomic analysis to investigate and characterize the possible molecular mechanisms of t...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/j.tox.2017.10.002
更新日期：2017-12-01 00:00:00
abstract：:Exposure of cultured rat mesangial cells to CdCl2 caused a dose- and time-dependent increase in intracellular glutathione that was significant at 0.5 microM and maximal at 1 microM Cd2+. The effect depended on glutathione synthesis and was masked by inhibiting synthesis with buthionine sulfoximine. The cells responded...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/0300-483x(93)90145-i
更新日期：1993-01-29 00:00:00
